Age associated losses of strength occur slowly over the adult lifespan. Most research has focused on what occurs in the elderly. However, the primary processes start at a much earlier age. In young and middle-aged workers, the early losses contribute to work related injuries and for some occupations, job performance. The causes of age related strength losses are multifactoral. Research has focused on age-associated loss of muscle that has been referred to as sarcopenia, While sarcopenia has been mainly studied in the elderly where the greatest changes in muscle mass and strength manifest, by age 50 the average individual has lost 10% of their maximal strength. While sarcopenia is clearly a major factor in strength loss, there are other contributors to the changes in maximal function. To understand sarcopenia these other factors need to be studied. Our goal is to understand the time course of strength loss, factors that contribute to the loss, the degree to which the exercise response differs between old and young individuals, and the forms of motivators and alternative exercise programs that might impact on the losses. We have used several different approaches to address these issues. First are descriptive studies using the Baltimore Longitudinal Study of Aging (BLSA). These studies focus on describing the characteristic losses that occur in muscle strength mass, and physical functioning that occur with aging by examining the entire adult lifespan and their impact on function and longevity. We have previously demonstrated that declining muscle strength and rate of change of muscle strength are independent contributors to mortality in men when considering age, physical activity and muscle mass. We have further shown that muscle power, and speed of movement are further independent sarcopenic factors that contribute to longevity. The observations suggest that central nervous system processes are contributing to the importance of sarcopenia on longevity. Second, working with collaborators at the University of Maryland, we are examining genetic contributions related to muscle hypertrophy and strength. We have identified several genes that contribute to the inherited aspects of how much muscle and strength we have. As an example, we reported that IGF-II genotype is related to muscle strength but not muscle mass. This is consistent with the mortality data, where muscle mass and muscle strength have common and different effects on outcome. Also, we found that IL6 and CNTF genotype had some influence on body composition which impacts on sarcopenia. Likewise, longer androgen receptor repeat in exon 1 in men is associated with higher testosterone blood levels and with greater levels of fat free mass. Third are intervention studies to alter the time course of strength and muscle mass changes. In previous work we demonstrated that the exercise response to resistive training is very similar in young and old subjects. However, while the response to strength training may be similar by age, there are clear differences in muscle responsiveness as represented by gene expression, and body compostion change differences. We have been interested in alternative strategies for exercise intervention. With Dr. Laura Talbot, we have examined two alternative exercise strategies using subjects with osteoarthritis of the knee. First was neuromuscular electrostimulation (NMES), a passive activation of the knee extensor muscles using an electric stimulator. We tested a protocol that used NMES at much lower force levels, to make the stimulation more acceptable (i.e. with less or no pain), and to minimize the likelihood of injury in individuals with osteoarthritis of the knee. The NMES group used a portable electrical muscle stimulator to incrementally increase the intensity of isometric contraction over 12 weeks up to 20-40% of their maximal voluntary strength. We found an increase in muscle strength in response to this passive activity, and a decline in knee pain immediately following the treatment (though not a sustained effect). The second approach was to use home based pedometer driven motivational program resulted in improved walking, increased knee extensor strength, and modest functional improvements. We are currently in the planning stages of a study to examine whether the use of electromyostimulation can positively impact the course of recovery from traumatic war-related below the knee amputation. During recovery and rehabilitation, quadriceps muscle strength declines following traumatic amputation. NMES may offer a passive form of exercise that can maintain strength during this time period.